Homo sapiens
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA296093 | ENA |
REPOSITORIES: ENA
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Project description:Following androgen ablation therapy (AAT), the vast majority of prostate cancer patients develop treatment resistance with a median time of 18-24 months to disease progression. To identify molecular targets that aid in prostate cancer cell survival and contribute to the androgen independent phenotype, we evaluated changes in LNCaP cell gene expression during 12 months of androgen deprivation. At time points reflecting critical growth and phenotypic changes, we performed Affymetrix expression array analysis to examine the effects of androgen deprivation during the acute response, during the period of apparent quiescence, and during the emergence of highly proliferative, androgen-independent prostate cancer cells (LNCaP-AI). We discovered alterations in gene expression for a host of molecules associated with promoting prostate cancer cell growth and survival, regulating cell cycle progression, apoptosis and adrenal androgen metabolism, in addition to AR co-regulators and markers of neuroendocrine disease. These findings illustrate the complexity and unpredictable nature of cancer cell biology and contribute greatly to our understanding of how prostate cancer cells likely survive AAT. The value of this longitudinal approach lies in the ability to examine gene expression changes throughout the cellular response to androgen deprivation; it provides a more dynamic illustration of those genes which contribute to disease progression in addition to specific genes which constitute a malignant androgen-independent phenotype. In conclusion, it is of great importance that we employ new approaches, such as the one proposed here, to continue exploring the cellular mechanisms of therapy resistance and identify promising targets to improve cancer therapeutics. Experiment Overall Design: To identify molecular targets that aid in prostate cancer cell survival and contribute to the androgen independent phenotype, we evaluated changes in LNCaP cell gene expression during 12 months of androgen deprivation. At time points reflecting critical growth and phenotypic changes, we performed Affymetrix expression array analysis to examine the effects of androgen deprivation during the acute response, during the period of apparent quiescence, and during the emergence of highly proliferative, androgen-independent prostate cancer cells (LNCaP-AI).
2008-04-07 | E-GEOD-8702 | biostudies-arrayexpress
Project description:Androgen deprivation is a standard of care front-line therapy for human prostate cancer, however, majority of patients will eventally develop resistance to androgen deprivation. In this study, using a human prostate cancer xenograft model -LuCaP35, we examiend the gene expression changes after castration.
2011-12-06 | GSE33316 | GEO
Project description:Androgen deprivation is a standard of care front-line therapy for human prostate cancer, however, majority of patients will eventally develop resistance to androgen deprivation. In this study, using a human prostate cancer xenograft model -LuCaP35, we examiend the gene expression changes after castration. We compare the gene expression of 5 LuCaP35 xenografts from non-treated mice (Control), and 5 androgen-deprived LuCaP35 xenografts from castrated mice (Castration).
2011-12-06 | E-GEOD-33316 | biostudies-arrayexpress
Project description:Castration-resistant prostate cancer (CRPC) emerges in response to androgen deprivation therapies and exhibits high cellular plasticity eventually progressing into neuroendocrine prostate cancer (NEPC). In this study, we took advantage of the dynamic prostate cancer cell system recapitulating the CRPC onset to identify lncRNAs induced early in response to androgen deprivation. In this system, first, adenocarcinoma LNCaP cells are grown in the presence of dihydrotestosterone (DHT) mimicking primary epithelial androgen-dependent luminal tumors (NE_0j). Then, they are subjected to androgen deprivation which induces immediate growth arrest, progressive change in cell morphology and properties towards the neuroendocrine-like phenotype (NE-like cells, NE_15j, 1m, 3m) and finally lead to acquisition of androgen independence (NE_6m). Total RNA-sequencing followed by differential expression analysis of scallop-assembled transcripts and multiple filtering isolated gencode annotated protein-coding and long noncoding RNA genes but also 15 novel lncRNAs highly upregulated upon androgen deprivation.
2025-10-13 | GSE267185 | GEO
Project description:Prostate cancer is a leading cause of cancer-related death and morbidity worldwide. Androgen deprivation therapy (ADT) is the cornerstone of management for advanced disease. The use of androgen deprivation therapies is associated with multiple side effects, including metabolic syndrome and truncal obesity. At the same time, obesity has been associated with both prostate cancer development and disease progression, linked to its effects on chronic inflammation at a tissue level. The connection between androgen deprivation therapy, obesity, inflammation, and prostate cancer progression is well-established in clinical settings; however, an understanding of the changes in adipose tissue at the molecular level induced by castrating therapies is missing. Here we investigated the transcriptional changes in periprostatic fat tissue induced by profound androgen deprivation therapy in a group of patients with high-risk tumours compared to a matching untreated cohort. We find that androgen deprivation therapy is associated with a pro-inflammatory and obesity-like adipose tissue microenvironment. This study suggests that the beneficial effect of androgen deprivation therapy may be partially counteracted by metabolic and inflammatory side effects in the adipose tissue surrounding the prostate.
| EGAS00001003286 | EGA
Project description:The effect of androgen deprivation on human prostate xenograft tumor LuCaP35
| PRJNA149301 | ENA
Project description:The ligand-activated androgen receptor is a transcription factor that drives prostate cancer growth. Blocking androgen-activation of androgen receptor via androgen deprivation therapy is the default treatment for metastatic prostate cancer. Despite initial remissions, androgen deprivation invariably fails and prostate cancer progresses to castration-recurrent disease, which still relies on aberrantly activated androgen receptor. Alternative approaches are needed to inhibit androgen receptor action in prostate cancer that has failed androgen deprivation therapy. Our laboratory has been exploring the therapeutic potential of a non-canonical androgen receptor signaling mechanism wherein androgen receptor stimulates another transcription factor, Serum Response Factor. Serum Response Factor-mediated androgen receptor action correlates with prostate cancer progression and is enriched in castration-recurrent prostate cancer. Inhibiting Serum Response Factor-dependent androgen receptor action may be an effective treatment strategy following failure of androgen deprivation therapy but remains poorly understood. We have recently isolated UPF1 and RCOR1 as putative novel mediators of Serum Response Factor-dependent androgen receptor action. Here, we perform RNA-Seq assays to determine the contribution of UPF1 and RCOR1 to the androgen response of prostate cancer cells.
2025-05-15 | GSE248034 | GEO
Project description:Increasing evidence indicates that minor subpopulations intrinsic to androgen-independence are present in prostate cancer cells, poised to become clonal dominance under prolonged androgen-deprivation selection. To stratify different subpopulations, we conduct transcriptome profiling of 144 single LNCaP prostate cancer cells treated and untreated with androgen after cell cycle synchronization. At least eight subpopulations of LNCaP cells are identified, revealing a previously unappreciable level of cellular heterogeneity to androgen stimulation. One subpopulation displays stem-like features, the advanced growth of which depends more on enhanced expression of 10 cell cycle-related genes and less on androgen-dependent signaling. Concordant upregulation of these genes appears to be linked to recurrent prostate cancers and can be used for early detection of tumors that subsequently develop androgen independence. Moreover, this single-cell approach provides a better understanding of how cancer cells respond heterogeneously to androgen-deprivation therapies and to reveal which subpopulations are resistant to this treatment.
2018-03-02 | GSE99795 | GEO
Project description:In analyzing transcriptomic data from a clinical trial of neoadjuvant-intensive Androgen Deprivation Therapy, we observed increased mRNA expression of the hallmark antiapoptotic gene BCL2 in the prostate tumors of treated patients versus those of untreated patients. We showed that BCL2 overexpressed LNCaP cells exhibited resistance to prolonged androgen deprivation therapy, indicating that BCL2-overexpression leads to castration resistance and cellular plasticity.Our study indicating that BCL2 overexpression may act as a major driver of early castration resistance in prostate cancer cells.
2025-05-15 | GSE273736 | GEO
Project description:Transcriptional profiling of human mesenchymal stem cells comparing normoxic MSCs cells with hypoxic MSCs cells. Hypoxia may inhibit senescence of MSCs during expansion. Goal was to determine the effects of hypoxia on global MSCs gene expression.
2011-02-19 | GSE20463 | GEO